This proposal is to request support for a Keystone Symposia meeting entitled "G Protein-Coupled Receptors: New Insights in Functional Regulation and Clinical Application", organized by Heidi E. Hamm, P. Jeffrey Conn, Jean-Phillippe Pin and Olivier Civelli, which will be held in Killarney, Ireland from May 18 - 23, 2008. The purpose of this meeting is to bring basic and clinical scientists together in order to open an insightful and productive dialogue about the future direction of this field and to help determine how academia and industry can mutually benefit from a more collaborative effort in applying what is learned in the laboratory to the application of better therapeutics in the clinic. The G-protein-coupled-receptor (GPCR) family accounts for almost 3% of the human genome and encompasses the largest number of receptors identified to date. Further, GPCRs have proven to be one of the primary targets for therapeutic drug intervention. Work in the field is rapidly progressing through the identification of structural aspects of activation, dimerization and its functional significance, ligand-directed signaling, de-orphanization of GPCRs and their signaling pathways, allosteric modulators of GPCR activation, as well as novel interacting protein complexes and their correlate signaling cascades. This Keystone Symposia meeting will focus on these important aspects of GPCRs as well as how they regulate functional systems such as sleep, stress and feeding. Finally, the effect of genetic disease on GPCR activation and signaling will be discussed. G protein-coupled receptors (GPCRs) are of utmost importance to drug discovery since they are the therapeutic targets for half of all prescribed drugs. We have reached a crucial point in the study of these receptors which requires an extensive collaborative effort between the academic laboratories in which the seminal discoveries are taking place and industry, where these discoveries are applied to the development of novel therapeutics to treat the numerous pathologies symptomatic of GPCR dysfunction. [unreadable] [unreadable] [unreadable]